PROJECT SUMMARY This renewal grant responds to BRG PAR-13-1371 for the development of noninvasive and nondestructive imaging methods for in vivo monitoring; novel diagnostic and medical devices; and new bioengineering ap- proaches to cardiovascular treatment. The grant targets atherosclerosis, which in advanced disease, is characterized by lesions with lipids, calcification, and fibrous caps whose rupture are a leading cause of stroke, heart attack and death. While typically diagnosed by X-ray catheterization, X-ray can't assess plaque contents, vulnerability to rupture, or early stage wall-thickening. Our goal is to develop a novel, safe, mini- mally-invasive, fast, high-resolution, cardiovascular imaging modality employing high-field intravascular (IV) magnetic resonance imaging (MRI), to assess and monitor disease, and provide targeted therapy delivery. In the expiring grant period we created novel dosimetry tools for testing the safety of internal devices dur- ing MRI. We showed theoretically and experimentally that the signal-to-noise ratio of internal detectors in- creased with MRI field strength-squared, at least up to 7 Tesla (T). This enabled 80m IVMRI at 3T and 40- 50m at 7T to visualize plaque morphology. We developed a new -imaging method, 'MRI endoscopy' that provides a stream of images intrinsically locked to the probe's viewpoint at up to 2 fr/s. Because IVMRI resolution at 40-50m is now within a range that could identify plaques vulnerable to rupture, and because chemically-selective imaging of mobile lipids is also possible at higher MRI fields, the possibility of character- izing key attributes of vulnerable plaque-thin fibrous caps and mobile lipid contents by IVMRI, now exists. But technical issues remain: we need still faster IVMRI, and reduced sensitivity to motion. We need a method of chemically selective IVMRI. We don't know how IVMRI compares with other IV modalities-IV ul- trasound (IVUS) or optical coherence tomography (OCT). And if we see disease, can we intervene? This re- newal addresses all these key questions. Aim 1 creates a high-speed real-time, motion-insensitive IVMRI capability using novel sparse sampling and frame-shifting methods. Aim 2 develops high-field 40-50m IV MRI and chemically-selective lipid imaging to characterize plaque caps and contents. Aim 3 performs com- parative studies in vitro and in vivo of IVMRI, OCT, and IVUS. Aim 4 creates an interventional platform for high-resolution IVMRI-targeting, demonstrated for angioplasty, and cellular and ultrasound ablation thera- pies. This project, supported by progress in the 1st grant and new preliminary work, can provide important new IV imaging and interventional tools to advance understanding and treatment of cardiovascular disease.